Citation and License

Genome Biology 2007, 8:R91
doi:10.1186/gb-2007-8-5-r91

Published: 25 May 2007

Abstract

Background

Down's syndrome (DS), or trisomy 21, is a complex developmental disorder that exhibits
many clinical signs that vary in occurrence and severity among patients. The molecular
mechanisms responsible for DS have thus far remained elusive. We argue here that normal
variation in gene expression in the population contributes to the heterogeneous clinical
picture of DS, and we estimated the amplitude of this variation in 50 mouse orthologs
of chromosome 21 genes in brain regions of Ts65Dn (a mouse model of DS). We analyzed
the RNAs of eight Ts65Dn and eight euploid mice by real-time polymerase chain reaction.

Results

In pooled RNAs, we confirmed that trisomic/euploid gene expression ratios were close
to 1.5. However, we observed that inter-individual gene expression levels spanned
a broad range of values. We identified three categories of genes: genes with expression
levels consistently higher in Ts65Dn than in euploids (9, 17, and 7 genes in cerebellum,
cortex, and midbrain, respectively); genes whose expression levels partially overlap
between the two groups (10, 9, and 14 genes); and genes with intermingled expression,
which cannot be used to differentiate trisomics from euploids (12, 5 and 9 genes).
Of the genes in the first category, App, Cbr1, and Mrps6 exhibited tight regulation in the three tissues and are therefore attractive candidates
for further research.

Conclusion

This is the first analysis addressing inter-individual gene expression levels as a
function of trisomy. We propose a strategy allowing discrimination between candidates
for the constant features of DS and those genes that may contribute to the partially
penetrant signs of DS.